The effects of lipids which accumulate in storage diseases were studied at the cellular level. Mouse macrophage (Mphi) cultures took up large amounts of glucocerebroside (GL1), a lipid which accumulates in Gaucher's disease. Consequently, Mphi exposed to GL1 released high levels of lysosomal enzymes and a mediator, lymphocyte activating factor (LAF). The interaction between GL1 and Mphi was found to be highly selective: (a) other storage lipids, like sphingomyelin or GM2 ganglioside, were taken up by Mphi to a much smaller amount than GL1 and had minimal or no effect on the release of Mphi products; (b) unlike Mphi, cultures of other cell types, lens epithelium or skin fibroblasts, failed to accumulate significant quantities of GL1. This selectivity in interaction between GL1 and Mphi in culture is in line with the exclusive accumulation of GL1 in Gaucher's patients, in Mphi of the reticuloendothelial system. In other experiments it was found that Mphi activated in vivo by bacteria or other agents lost considerably their capacity to accumulate GL1 and to release products when incubated with this lipid. GL1 may be useful, therefore, in differentiating between untreated and activated Mphi.